Aromatase and estrogen 2-hydroxylase activities of human placental microsomes in pregnancy-induced hypertension.

Abstract

2-Hydroxylation is one of the major metabolic pathways of estrogens and is believed to be catalyzed by a form of cytochrome P450. Recently it has been reported that estrogen 2-hydroxylase activity in human placenta is catalyzed by aromatase. Some investigators suggested the effect of catechol estrogen on human placental steroidogenesis which may be related to pregnancy-induced hypertension (PIH) through the inhibition of catechol-O-methyltransferase (COMT) activity. In order to better understand the interrelationship between placental aromatase and estrogen 2-hydroxylase activities in PIH patients, both activities were evaluated in the PIH placentas. Human placental microsomes obtained from PIH patients were incubated with [1 beta-3H]androstenedione or [2-3H]estradiol in the presence of NADPH. Aromatase and estrogen 2-hydroxylase activities were assessed by the tritium water method. The immunosuppression patterns of both activities due to monoclonal antiaromatase cytochrome P450 antibody (MAb3-2C2) were studied. Estrogen 2-hydroxylase activity was significantly higher in PIH placentas (4.7 +/- 0.9 pmol/min/mg protein, n = 7) than in normal placentas (3.0 +/- 0.7 pmol/min/mg protein, n = 7). When the PIH placental microsomes were subjected to immunosuppression by 1 to 100 micrograms IgG of MAb3-2C2, estrogen 2-hydroxylase activity was suppressed by 94 to 65% whereas aromatase activity was strongly suppressed by 72 to 17%, respectively. From our results of high estrogen 2-hydroxylase activity in PIH placentas, it is assumed that there is a different estrogen catalyzing mechanism in PIH placentas.

• Authors: K Okubo, M Jinbo, Y Toma, Y Shimizu, T Yanaihara
• Journal: Endocrine journal (Endocr J) Vol. 43 Issue 4 Pg. 363-8 (Aug 1996) ISSN: 0918-8959 [Print] Japan
• PMID: 8930523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Aromatase Inhibitors
• Enzyme Inhibitors
• Estradiol
• Cytochrome P-450 Enzyme System
• Steroid Hydroxylases
• Aromatase
• Cytochrome P-450 CYP1A1
• estrogen 2-hydroxylase

Topics

• Antibodies, Monoclonal (pharmacology)
• Aromatase (metabolism)
• Aromatase Inhibitors
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 Enzyme System (metabolism)
• Enzyme Inhibitors (pharmacology)
• Estradiol (metabolism)
• Female
• Fetal Growth Retardation (enzymology)
• Humans
• Hypertension (enzymology)
• Kinetics
• Microsomes (enzymology)
• Placenta (enzymology, ultrastructure)
• Pregnancy
• Pregnancy Complications, Cardiovascular (enzymology)
• Steroid Hydroxylases (metabolism)